Fig 1
Control of cell-cycle progression by Hog1. The cyclin-dependent kinase (CDK) Cdc28 associates with phase-specific cyclins (shown around the central circle) to regulate passage through the cell cycle (G1 → S → G2 → M). Upon stress, Hog1 modulates progression at all phases of the cell cycle by acting on core elements of the cell cycle machinery
Source publication
Eukaryotic cells have developed sophisticated systems to constantly monitor changes in the extracellular environment and to orchestrate a proper cellular response. To maximize survival, cells delay cell-cycle progression in response to environmental changes. In response to extracellular insults, stress-activated protein kinases (SAPKs) modulate cel...
Citations
... Osmostress-activated protein kinase Hog1 orchestrates the cellular response to perturbations in osmotic conditions by activating a variety of transcription factors. Together with these transcription factors, Hog1 binds directly to the promoters of target genes to stimulate their transcription initiation and elongation [137]. An important part of the Hog1-mediated stress response is the inhibition of the cell cycle through activation of inhibitors of Cdc28, a cyclin-dependent kinase (CDK) that controls cell cycle progression in S. cerevisiae. ...
... Thus, Hog1 inhibits Cdc28 at the protein level but induces the expression of CDC28. These seemingly opposing processes lead to cell cycle arrest but prepare the cell for re-entry into the cell cycle once it adapts to stress or the conditions become favourable again [137]. of its 3 kb promoter. Its transcription interferes with the transcription of FLO11 and is negatively regulated by the transcription of the second lncRNA PWR1, which is expressed from the opposite strand and partially overlaps ICR1. ...
Cells must change their properties in order to adapt to a constantly changing environment. Most of the cellular sensing and regulatory mechanisms described so far are based on proteins that serve as sensors, signal transducers, and effectors of signalling pathways, resulting in altered cell physiology. In recent years, however, remarkable examples of the critical role of non-coding RNAs in some of these regulatory pathways have been described in various organisms. In this review, we focus on all classes of non-coding RNAs that play regulatory roles during stress response, starvation, and ageing in different yeast species as well as in structured yeast populations. Such regulation can occur, for example, by modulating the amount and functional state of tRNAs, rRNAs, or snRNAs that are directly involved in the processes of translation and splicing. In addition, long non-coding RNAs and microRNA-like molecules are bona fide regulators of the expression of their target genes. Non-coding RNAs thus represent an additional level of cellular regulation that is gradually being uncovered.
... The upregulated genes, sho1 and sln1, with the help of the activation of upstream control gene ste20 and ypd1, recognized as an activator of HOG-MAPK, led to the decreased transcriptional level of hog1 (Fig. 6c). Environmental stress induces cell-cycle delays, which announce cells to adapt to the stress before progressing into vulnerable cell cycle transitions (53,54). Here, we found that the morphogenesis checkpoint regulated by hog1 was the dominant "control" part, which made the G2/M phase of the cell cycle unable to proceed normally. ...
High hydrostatic pressure (HHP) influences the life processes of organisms living at depth in the oceans. While filamentous fungi are one of the essential members of deep-sea microorganisms, few works have explored their piezotolerance to HHP. Here, we obtained three homogeneous Aspergillus sydowii from terrestrial, shallow, and hadal areas, respectively, to compare their pressure resistance. A set of all-around evaluation methods including determination of growth rate, metabolic activity, and microscopic staining observation was established and indicated that A. sydowii DM1 from the hadal area displayed significant piezotolerance. Global analysis of transcriptome data under elevated HHP revealed that A. sydowii DM1 proactively modulated cell membrane permeability, hyphae morphology, and septal quantities for seeking a better livelihood under mild pressure. Besides, differentially expressed genes were mainly enriched in the biosynthesis of amino acids, carbohydrate metabolism, cell process, etc., implying how the filamentous fungi respond to elevated pressure at the molecular level. We speculated that A. sydowii DM1 could acclimatize itself to HHP by adopting several strategies, including environmental response pathway HOG-MAPK, stress proteins, and cellular metabolisms.
IMPORTANCE
Fungi play an ecological and biological function in marine environments, while the physiology of filamentous fungi under high hydrostatic pressure (HHP) is an unknown territory due to current technologies. As filamentous fungi are found in various niches, Aspergillus sp. from deep-sea inspire us to the physiological trait of eukaryotes under HHP, which can be considered as a prospective research model. Here, the evaluation methods we constructed would be universal for most filamentous fungi to assess their pressure resistance, and we found that Aspergillus sydowii DM1 from the hadal area owned better piezotolerance and the active metabolisms under HHP indicated the existence of undiscovered metabolic strategies for hadal fungi. Since pressure-related research of marine fungi has been unexpectedly neglected, our study provided an enlightening strategy for them under HHP; we believed that understanding their adaptation and ecological function in original niches will be accelerated in the perceivable future.
... Thus, the evolution of temporal gene expression dynamics when both the evolutionary and developmental timescale are comparatively short remains relatively unexplored. Moreover, these studies have focused almost exclusively on protein coding genes (for exceptions see: [20,23]), missing the potential contribution of non-coding genes, such as long non-coding RNAs (lncRNAs), which have emerged as important regulators of gene expression in the last decade [35] and have been shown to contribute to adaptation [36][37][38]. ...
Gene expression variation is pervasive across all levels of organismal organization, including development. Few studies, however, have examined variation in developmental transcriptional dynamics among populations, or how it contributes to phenotypic divergence. Indeed, the evolution of gene expression dynamics when both the evolutionary and temporal timescale are comparatively short remains relatively uncharacterized. Here, we examined coding and non-coding gene expression in the fat body of an ancestral African and a derived European Drosophila melanogaster population across three developmental stages spanning ten hours of larval development. Between populations, expression divergence was largely stage-specific. We detected higher expression variation during the late wandering stage, which may be a general feature of this stage. During this stage, we also detected higher and more extensive lncRNA expression in Europe, suggesting that lncRNA expression may be more important in derived populations. Interestingly, the temporal breadth of protein-coding and lncRNA expression became more restricted in the derived population. Taken together with the signatures of potential local adaptation that we detected at the sequence level in 9-25% of candidate genes (those showing evidence of expression divergence between populations), this finding suggests that gene expression becomes more developmental stage-specific during adaptation to new environments. We further used RNAi to identify several candidate genes that likely contribute to known phenotypic divergence between these populations. Our results shed light on the evolution and dynamics of expression variation over short developmental and evolutionary timescales, and how this variation contributes to population and phenotypic divergence.
... Like other LncRNAs, TERRA seems to also play a central role in the regulation of other aspects of cell biology. In fact, the expression of many LncRNAs can change in response to stress adaptation [109]. More specifically, in mammalian cells, TERRA has been found in the extracellular inflammatory exosomes outside of the nucleus, playing a role in stimulating immune signaling, and was proposed as a marker revealing telomeric dysfunction during diseases [110,111]. ...
Telomeres are structures made of DNA, proteins and RNA found at the ends of eukaryotic linear chromosomes. These dynamic nucleoprotein structures protect chromosomal tips from end-to-end fusions, degradation, activation of damage checkpoints and erroneous DNA repair events. Telomeres were thought to be transcriptionally silent regions because of their constitutive heterochromatin signature until telomeric long non-coding RNAs (LncRNAs) were discovered. One of them, TERRA (TElomeric Repeat-containing RNA), starts in the subtelomeric regions towards the chromosome ends from different telomeres and has been extensively studied in many evolutionarily distant eukaryotes. Changes in TERRA’s expression can lead to telomeric dysfunction, interfere with the replicative machinery and impact telomere length. TERRA also co-localizes in vivo with telomerase, and can form RNA:DNA hybrid structures called R-loops, which have been implicated in the onset of senescence and the alternative lengthening of telomere (ALT) pathway. Yet, the molecular mechanisms involving TERRA, as well as its function, remain elusive. Here, we review the current knowledge of TERRA transcription, structure, expression, regulation and its multiple telomeric and extra-telomeric functions in the budding yeast Saccharomyces cerevisiae.
... LncRNAs were once considered to be noises in transcriptional processes. However, previous studies have demonstrated that lncRNAs participate in various biological processes, such as cell proliferation, cell death, cell differentiation and cell cycle regulation (22)(23)(24)(25)(26). Moreover, lncRNAs are closely correlated with the occurrence of diseases, such as atherosclerosis, Parkinson's disease and cancers (27)(28)(29). ...
Long non-coding RNAs (lncRNAs) are involved in the gene expression regulation and usually play important roles in various human cancers, including the renal cell carcinoma (RCC). Dysregulation of certain lncRNAs are associated with the prognosis of patients with RCC. In the present review, several recently studied lncRNAs were discussed and their critical roles in proliferation, migration, invasion, apoptosis and drug resistance of renal cancer cells were revealed. The research on lncRNAs further increases our understanding on the development and progression of RCC. It is suggested that lncRNAs can be used as biomarkers or therapeutic targets for diagnosis or treatment of renal cancer.
... Cell cycle was also severely influenced by saturated NaCl concentration. Cell cycle arrest is a well-documented strategy in yeasts and filamentous fungi to contend with hyperosmolarity (Solé et al., 2014). In the presence of different stimuli (i.e., osmostress), cells must delay the cell cycle progression to allow the adaptive responses to the new environmental conditions before cells trigger vulnerable cell-cycle transition periods. ...
Although various studies have investigated osmoadaptations of halophilic fungi to saline conditions, only few analyzed the fungal mechanisms occurring at saturated NaCl concentrations. Halophilic Aspergillus sydowii is a model organism for the study of molecular adaptations of filamentous fungi to hyperosmolarity. For the first time a multi-omics approach (i.e., transcriptomics and metabolomics) was used to compare A. sydowii at saturated concentration (5.13 M NaCl) to optimal salinity (1 M NaCl). Analysis revealed 1,842 genes differentially expressed of which 704 were overexpressed. Most differentially expressed genes were involved in metabolism and signal transduction. A gene ontology multi-scale network showed that ATP binding constituted the main network node with direct interactions to phosphorelay signal transduction, polysaccharide metabolism, and transferase activity. Free amino acids significantly decreased and amino acid metabolism was reprogrammed at 5.13 M NaCl. mRNA transcriptional analysis revealed upregulation of genes involved in methionine and cysteine biosynthesis at extreme water deprivation by NaCl. No modifications of membrane fatty acid composition occurred. Upregulated genes were involved in high-osmolarity glycerol signal transduction pathways, biosynthesis of β-1,3-glucans, and cross-membrane ion transporters. Downregulated genes were related to the synthesis of chitin, mannose, cell wall proteins, starvation, pheromone synthesis, and cell cycle. Non-coding RNAs represented the 20% of the total transcripts with 7% classified as long non-coding RNAs (lncRNAs). The 42% and 69% of the total lncRNAs and RNAs encoding transcription factors, respectively, were differentially expressed. A network analysis showed that differentially expressed lncRNAs and RNAs coding transcriptional factors were mainly related to the regulation of metabolic processes, protein phosphorylation, protein kinase activity, and plasma membrane composition. Metabolomic analyses revealed more complex and unknown metabolites at saturated NaCl concentration than at optimal salinity. This study is the first attempt to unravel the molecular ecology of an ascomycetous fungus at extreme water deprivation by NaCl (5.13 M). This work also represents a pioneer study to investigate the importance of lncRNAs and transcriptional factors in the transcriptomic response to high NaCl stress in halophilic fungi.
... LncRNAs are also involved in the stress response of marine organisms; a previous studies characterized the role of lncRNAs in the responses of sea cucumber to environmental stress, and it was found that lncRNAs are involved in pathways such as the cell cycle, immunity, and energy metabolism (Huo et al., 2020). They are also involved in the regulation of cell cycle progression and stress adaptation (Solé et al., 2015;Zhang et al., 2014). Several studies examining the role of lncRNAs in scleractinian coral have been published recently Mohamed et al., 2016). ...
Some scleractinian corals exhibit high thermal adaptability to climate changes, although the mechanism of their adaptation is unclear. This study investigated the adaptability of scleractinian coral Pocillopora damicornis to thermally variable reef environments by applying a nanopore-based RNA sequencing method to characterize different transcription responses that promote heat tolerance of P. damicornis. We identified 1,414 novel genes and optimized 6,256 mis-annotated loci. Based on full-length transcriptome data, we identified complex alternative polyadenylation and alternative splicing events, which can improve our understanding of the genome annotation and gene structures of P. damicornis. Furthermore, we constructed differentially expressed lncRNA-mRNA co-expression networks, which may play a crucial role in the P. damicornis thermal adaptive response. KEGG function enrichment analysis revealed that P. damicornis from the high-temperature pool had a lower metabolic rate than that from the low-temperature pool. We hypothesize that metabolic readjustment, in the form of a lower metabolic rate, positively correlated with increased heat tolerance in P. damicornis in thermally variable reef environments. Our study provides novel insights into lncRNAs that promote thermally tolerance of scleractinian corals in the thermally variable reef environment, suggesting potential mechanisms for their adaptation to global warming in the future.
... Stress restricts cell cycle progression, and budding yeast cells display a diverse set of mechanisms as a function of the stress signal. The HOG pathway constitutes a prominent paradigm and operates on specific molecular targets to modulate different cell cycle phases and transitions in response to osmotic stress (Solé et al., 2015;de Nadal et al., 2011). Regarding entry into the cell cycle, osmotic shock causes a temporary repression of the G1/S regulon (Bellí et al., 2001), in which Hog1-mediated phosphorylation of Whi5 and Msa1 contributes to inhibiting transcription (González-Novo et al., 2015). ...
Stress granules (SGs) are conserved biomolecular condensates that originate in response to many stress conditions. These membraneless organelles contain nontranslating mRNAs and a diverse subproteome, but our knowledge of their regulation and functional relevance is still incipient. Here, we describe a mutual-inhibition interplay between SGs and Cdc28, the budding yeast Cdk. Among Cdc28 interactors acting as negative modulators of Start, we have identified Whi8, an RNA-binding protein that localizes to SGs and recruits the mRNA of CLN3, the most upstream G1 cyclin, for efficient translation inhibition and Cdk inactivation under stress. However, Whi8 also contributes to recruiting Cdc28 to SGs, where it acts to promote their dissolution. As predicted by a mutual-inhibition framework, the SG constitutes a bistable system that is modulated by Cdk. Since mammalian cells display a homologous mechanism, we propose that the opposing functions of specific mRNA-binding proteins and Cdk’s subjugate SG dynamics to a conserved hysteretic switch.
... Additional mechanisms of cell cycle progression upon stress will appear, some of them by using strategies that are qualitatively different to targeting particular activators or inhibitors and that rather modulate more general machineries. The use of cutting-edge technologies and approaches are starting to reveal mechanisms such as the regulation exerted by the HOG pathway on the antisense RNA of the CDK Cdc28 upon osmostress [161,162]. Taken together, the new knowledge gained will provide a comprehensive view of cell cycle regulation by osmostress and more generally by external modulators. ...
During evolution, cells have developed a plethora of mechanisms to optimize survival in a changing and unpredictable environment. In this regard, they have evolved networks that include environmental sensors, signaling transduction molecules and response mechanisms. Hog1 (yeast) and p38 (mammals) stress-activated protein kinases (SAPKs) are activated upon stress and they drive a full collection of cell adaptive responses aimed to maximize survival. SAPKs are extensively used to learn about the mechanisms through which cells adapt to changing environments. In addition to regulating gene expression and metabolism, SAPKs control cell cycle progression. In this review, we will discuss the latest findings related to the SAPK-driven regulation of mitosis upon osmostress in yeast.
... Eukaryotic cells have developed sophisticated systems to constantly monitor changes in the extracellular environment and to orchestrate proper cellular responses so as to accomplish stress adaptation. To maximize survival, cells delay cell-cycle progression in response to environmental insults [124]. Activation of stress responses can induce diverse physiological changes, including modulation of cell cycle progression [125] and excessive stress on replication occasions mitotic cell death [126,127]. ...
Trichothecium roseum is a harmful postharvest fungus causing serious damage, together with the secretion of insidious mycotoxins, on apples, melons, and other important fruits. Cuminal, a predominant component of Cuminum cyminum essential oil has proven to successfully inhibit the growth of T. roseum in vitro and in vivo. Electron microscopic observations revealed cuminal exposure impaired the fungal morphology and ultrastructure, particularly the plasmalemma. Transcriptome and proteome analysis was used to investigate the responses of T. roseum to exposure of cuminal. In total, 2825 differentially expressed transcripts (1516 up and 1309 down) and 225 differentially expressed proteins (90 up and 135 down) were determined. Overall, notable parts of these differentially expressed genes functionally belong to subcellular localities of the membrane system and cytosol, along with ribosomes, mitochondria and peroxisomes. According to the localization analysis and the biological annotation of these genes, carbohydrate and lipids metabolism, redox homeostasis, and asexual reproduction were among the most enriched gene ontology (GO) terms. Biological pathway enrichment analysis showed that lipids and amino acid degradation, ATP-binding cassette transporters, membrane reconstitution, mRNA surveillance pathway and peroxisome were elevated, whereas secondary metabolite biosynthesis, cell cycle, and glycolysis/gluconeogenesis were down regulated. Further integrated omics analysis showed that cuminal exposure first impaired the polarity of the cytoplasmic membrane and then triggered the reconstitution and dysfunction of fungal plasmalemma, resulting in handicapped nutrient procurement of the cells. Consequently, fungal cells showed starvation stress with limited carbohydrate metabolism, resulting a metabolic shift to catabolism of the cell’s own components in response to the stress. Additionally, these predicaments brought about oxidative stress, which, in collaboration with the starvation, damaged certain critical organelles such as mitochondria. Such degeneration, accompanied by energy deficiency, suppressed the biosynthesis of essential proteins and inhibited fungal growth.
